Program Director/Principal Investigator: Govindarkarnavar, Arunkumar ABSTRACT Emerging and re-emerging infectious diseases may present as acute febrile illness (AFI), which is associated with considerable morbidity and mortality and poses a potentially huge economic burden. Clinical diagnosis of these fevers is often not performed or is elusive. Laboratory-based disease diagnosis is critical for appropriate treatment and response, resource allocation and prioritization of prevention, detection and control of infectious diseases. The sentinel hospital based AFI surveillance in India established under the Global Health Security Agenda (GHSA) from 2014 to 2018 gave a baseline data on the etiology of AFI in India. Laboratory examination of 38000 cases from 32 sentinel hospitals across ten states on India recorded an etiology in around 50% cases. Among these 50%, the major etiologies of AFI consist of influenza (31%), dengue (14%), scrub typhus (9%), leptospirosis (8%), malaria (6%) and Kyasanur Forest Disease (4%). Influenza was found across the country in a considerably large proportion (31%). The study also helped in establishing the incidence of scrub typhus as a major contributor (9%) of the AFI cases. Also, a significant proportion of AFIs (52%) remain undiagnosed. Risk factors for these infections or disease outcomes couldn?t be studied in this programme. Building on the findings of the AFI surveillance, we propose to establish geographically representative cohorts of AFI based at a select number of established sites. These cohorts will facilitate the study of risk factors specific to each of the major etiologies of AFI thereby generating evidence based recommendations for active prevention and control of specific illnesses. The activities proposed in this project also aim to identify disease burden and generate information regarding the health utilization behaviors of various populations through establishing Demographic Surveillance System (DSS) sites. We will also focus on identifying the etiologies of the large proportion of unknown pathogens causing AFI using advanced pathogen discovery techniques including next generation sequencing. The study activities will also include laboratory strengthening activities at the district level, including training and capacity building, which aims to enhance the diagnostic capacity of the existing public health laboratories for major etiologies of AFI. The project will strengthen the existing relationship with national and state health systems thereby creating an environment of synergy and cooperation in disease surveillance activities across the country. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Continuation Format Page